Approximately 40% of the world's population lives in areas where a significant risk of contracting malaria exists. Each year, 300-500 million people suffer from acute malaria, and 0.5-2.5 million die from the disease. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise. The most important reason for this alarming situation is the rapid spread of malaria parasites that are resistant to antimalarial drugs, especially chloroquine, which is by far the most frequently used.
The research and development of new antimalarial drugs has been largely neglected since the 1970s owing to the end of colonialism, changes in the areas of military engagement, and the restricted market potential. Currently, few drugs against the malaria liver stage parasites are available. Because of technical difficulties, low yield and the complexity of the setting necessary to produce liver stage parasites, no new drugs are assessed systematically against these stages. Nevertheless, liver stages are a strong potential for drug targeting because; a) they possess a more complex and distinct metabolism than their blood stage counterpart, and b) they precede the pathogenic blood stage and thus offer prophylactic possibilities against malaria. Thus, the evaluation of new drugs against the liver stage offers new therapeutic horizons.
An additional observation is that some antimalarial compounds, for example, chloroquine also exhibit anti-HIV-1 activity. (See, for example, Savarino A, Gennero L, Chen H C, Serrano D, Malavasi F, Boelaert J R, Sperber K. Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum of activity. AIDS 2001 Nov. 23; 15(17):2221-9; Savarino A, Gennero L, Sperber K, Boelaert J R. The anti-HIV-1 activity of chloroquine. J Clin Virol 2001 February; 20(3):131-5.
Thus, the need in society exists for new therapeutics, which demonstrate advantageous clinical efficacy for the treatment and/or prevention of malaria, as well as for drugs that may be useful for the treatment and/or prevention of HIV infection and/or AIDS.